We propose to pursue our studies of the role of the glucocorticoid receptor in the mechanism of the production of cleft palate in various strains of mice by glucocorticoids and phenytoin. The hypothesis to be tested is that the teratogenic action of glucocorticoids is mediated by an H-2-influenced receptor which binds both glucocorticoids and phenytoin. This receptor mediates both the teratogenic and antiinflammatory actions of glucocorticoids. These actions involve the production of phospholipase A2-inhibitory proteins (PLIPs), which inhibit the release of arachidonic acid and the subsequent production of prostaglandins. We propose to 1) to study the development of glucocorticoid receptors IB and II in embryonic palates, 2) to measure the levels of IB and II in embryonic palates of congenic mouse strains with high and low susceptibility to cortisone-induced cleft palate, 3) to conduct a Mendelian experiment to determine whether receptor IB is controlled by an H-2-linked gene (in collaboration with Dr. David L. Gasser), 4) to study the properties and to measure the level of IB in visceral yolk sacs of congenic mouse strains with high and low susceptibility to cortisone-induced palate to determine whether this tissue has only receptor IB binding glucocorticoids and phenytoin (DPH) and whether there is a H-2-linked difference in the level of IB in this tissue, 5) to determine the ability of glucocorticoids and DPH to inhibit the release of arachidonic acid in visceral yolk sacs of congenic mouse strains with high and low susceptibility to cortison-induced cleft palate, and 6) to determine the ability of glucocorticoids and DPH to produce phospholipase-inhibitory proteins (PLIPs) in visceral yolk sacs of congenic mouse strains with high and low susceptibility to cortisone-induced cleft palate.